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Literature detail

Structural basis of receptor recognition by SARS-CoV-2.

Jian Shang1 Gang Ye1 Ke Shi2 Yushun Wan1 Chuming Luo1 Hideki Aihara2 Qibin Geng1 Ashley Auerbach1 Fang Li3
Affiliations 3 institutions
  1. Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA.
  2. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  3. Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA. [email protected].
PMID 32225175 2020 Nature eng ppublish
PubMed DOI Browse context

Article

Publication summary

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-19<sup>1,2</sup>. A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans<sup>3,4</sup>. Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.

Angiotensin-Converting Enzyme 2 Animals Betacoronavirus Binding Sites China Chiroptera Coronavirus Coronavirus Infections COVID-19 Crystallization Crystallography, X-Ray Disease Reservoirs Eutheria Humans Models, Molecular Pandemics Peptidyl-Dipeptidase A Pneumonia, Viral

Structured evidence records

Evidence records

6 total
Receptor Usage 3 records
Receptor Usage Extraction confidence 1.00
Key finding

SARS-CoV-2 spike RBD binds human ACE2 as its receptor, with structural evidence confirming receptor usage and interaction details.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans. Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 in complex with ACE2.

Method
crystal structure determination
Receptors
ACE2
Receptor Usage Extraction confidence 1.00
Key finding

The bat coronavirus RaTG13 can use human ACE2 as its receptor, demonstrating receptor compatibility across species.

Virus
SARSr-CoV
Location
Not specified
Supporting text

Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor.

Receptors
ACE2
Receptor Usage Extraction confidence 1.00
Key finding

SARS-CoV uses human ACE2 as its receptor, consistent with receptor usage shared with SARS-CoV-2.

Virus
SARS-CoV
Location
Not specified
Supporting text

SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans.

Receptors
ACE2
Molecular Adaptation 2 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Residue changes in the SARS-CoV-2 spike RBD enhance ACE2 binding affinity, indicating molecular adaptation for receptor recognition and host range expansion to humans.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

We determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity.

Genes or proteins
spike; RBD
Receptors
ACE2
Mechanism types
receptor_binding; cell_entry; host_range
Molecular Adaptation Extraction confidence 0.90
Key finding

RaTG13, a bat coronavirus related to SARS-CoV-2, can engage human ACE2, demonstrating molecular adaptation in receptor usage that may facilitate cross-species transmission.

Virus
SARSr-CoV
Host
Not specified
Location
Not specified
Supporting text

Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2.

Genes or proteins
spike; RBD
Receptors
ACE2
Mechanism types
receptor_binding; cell_entry; cross_species_adaptation
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.90
Key finding

Comparative sequence and structural analysis of the spike RBDs revealed residue changes distinguishing SARS-CoV-2 from SARS-CoV and the bat coronavirus RaTG13, demonstrating evolutionary differences underlying receptor recognition.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor.

Genes or proteins
spike; receptor-binding domain (RBD)
Analysis methods
comparative structural analysis; sequence comparison